Michael DaSilva1, Alyssa Macbeth1, Steven Harrison1, Betty Wolff1, Maegan Harden1, Gina Vicente1, Sarah Babchuck1, Katelyn Flowers1, Kunsang Gyaltsen1, Brian Granger1, George Grant1, Heidi Rehm1, Stacey Gabriel1, Niall Lennon1
1Broad Institute of MIT and Harvard, Cambridge, MA
As the utility of genomics evolves, a need has emerged for large-scale genomic datasets produced in a clinical setting. To satisfy that niche, the Genomics Platform at the Broad Institute has established CAP/CLIA compliant genotyping capabilities at scale. Once such effort requiring these capabilities is the All of Us research project (AoURP). Funded by the National Institutes of Health (NIH), AoURP aims to generate sequencing and genotyping data from 1 million or more research participants across the U.S. Medically actionable results from a pre-defined set of genes (termed the AoU Medically Actionable Panel, AoUMAP) will be returned to participants after orthogonal validation in a clinical validation laboratory. Genotyping will be run using the Illumina All of Us (AoU) array that has been specifically designed with 1.8 million markers across the human genome. AoU array content has been designed to capture pathogenic and likely pathogenic sites (as defined by ClinVar) across the AoUMAP, in addition to pharmacogenetic markers.
As one of three Genome Centers selected by the AoURP program, the Broad Institute Genomics Platform has built the operational and clinical infrastructure required to genotype >300,000 AoURP participants over the next 4-5 years. We performed an analytical validation study to assess the accuracy and precision of the AoU Array. A combination of reference samples, PGx cell lines, and previously tested clinical samples were used to verify that the array is suitable for its intended use as part of the AoURP. In addition, we have established the capacity to meet AoURP scale, while running other concurrent, large-scale projects.
Here we discuss the onboarding process for the new array, the establishment of CLIA/CAP quality standards in our genotyping process, and the results of our analytical validation study.